Corporate Presentation - November 2019 - Liminal BioSciences Inc. (NASDAQ: LMNL, TSX:LMNL) - Jefferies
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
Liminal BioSciences Inc. (NASDAQ: LMNL, TSX:LMNL) Corporate Presentation – November 2019
Safe Harbour
Forward Looking Statement
This presentation contains forward-looking statements about Liminal BioSciences’ objectives, strategies and businesses that involve risks and uncertainties. These statements are “forward-looking” because
they are based on our current expectations about the markets we operate in and on various estimates and assumptions. Forward looking statements are subject to a number of risks, uncertainties and
assumptions. Moreover, Liminal BioSciences operates in a very competitive and rapidly changing environment. New risks emerge from time to time. It is not possible for Liminal BioSciences' management
to predict all risks, nor can Liminal BioSciences assess the impact of all factors on its business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from
those contained in any forward looking statements it may make. Actual events or results may differ materially from those anticipated in these forward-looking statements if known or unknown risks affect
our business, or if our estimates or assumptions turn out to be inaccurate. Such risks and assumptions include, but are not limited to statements concerning the outcome or success of Liminal BioSciences'
clinical trials, its ability to successfully gain regulatory approvals and commercialize products, its ability to successfully advance its pipeline of product candidates, the potential benefits of strategic
collaboration agreements and its ability to enter into strategic arrangements or collaborations, the rate and degree of market acceptance of its products, its ability to develop sales and marketing
capabilities, the closing of the share purchase agreement for the divestment of Prometic Bioseparations Ltd., the availability of funds and resources to pursue R&D projects, the ability of Liminal to take
advantage of business opportunities in the pharmaceutical industry, uncertainties related to the regulatory process and general changes in economic conditions. You will find a more detailed assessment of
the risks that could cause actual events or results to materially differ from our current expectations in the Annual Information Form for the year ended December 31, 2018, under the heading “Risk
Factors”. As a result, we cannot guarantee that any forward-looking statement will materialize. Although Liminal BioSciences believes that the expectations reflected in the forward looking statements are
reasonable, it cannot guarantee that the future results, levels of activity, performance or events and circumstances reflected in the forward looking statements will be achieved or occur. Moreover, except
as required by law, neither Liminal BioSciences nor any other person assumes responsibility for the accuracy and completeness of the forward looking statements. Forward looking statements in this
presentation represent Liminal BioSciences' views only as of the date of this presentation. We assume no obligation to update or review any forward-looking statement even if new information becomes
available, as a result of future events or for any other reason, unless required by applicable securities laws and regulations. All amounts are in Canadian dollars unless indicated otherwise.
Copyright notice
The information contained in this presentation (including names, images, logos and descriptions portraying Liminal BioSciences’ products and/or services) is the property of Liminal BioSciences Inc., of its
divisions and / or of its subsidiaries (“Liminal”) and is protected by copyright, patent and trademark law and / or other intellectual property rights. Neither this presentation nor any part may be
reproduced or transmitted in any form or by any means, electronic or mechanical, including printing and photocopying, or by any information storage or retrieval system without prior permission in writing
from Liminal.
Disclaimer
Liminal reserves the right to make improvements, corrections and/or changes to this presentation at any time.
2
© 2019 Liminal BioSciences Inc.
Liminal BioSciences Inc.
Investment Highlights: LMNL
• Trading commenced on the Nasdaq Global Market on Nov 18, 2019 (cross-listed on TSX)
• 25 year old biotech undergoing significant strategic transformation to simplify operations, achieve financial stability
and focus R&D on small molecule therapeutics
• Filing of amended BLA expected in 1H-2020 for Ryplazim™ for treatment of congenital plasminogen deficiency
• Current R&D focus on novel targets for treatment of serious fibrosis in respiratory, liver and kidney disease with
expected expansion of R&D portfolio through collaboration, in-licensing and acquisition
• Current financial position : USD$ 85 MM in new equity financing in Q2-2019, pending sale of PBL division to KKR
and expected Ryplazim™ marketing partnership
• Supportive majority stockholder in Thomvest, a private investment affiliate of the Thomson family
• 350 employees located in Canada, USA and UK
3
© 2019 Liminal BioSciences Inc.
Drive preclinical and clinical development of
multiple compounds in specific indications of Priority focus on rare and orphan
interest in fibrosis in respiratory, liver and diseases
kidney diseases
Expand our research engine beyond
FFAR’s through licensing, acquisition Initiate Phase 2 and 3 clinical
and early-stage research Our Focus studies for PBI-4050 in 2020
collaborations
Opportunistic partnering and
Add to our current talent hubs in
divestiture for other products and
Canada, USA and UK
businesses outside of small
molecule therapeutics
4
© 2019 Liminal BioSciences Inc.
Recent Achievements
2019 2019 2019 2019 2019
New capital structure Revitalized leadership Rebranding and name Pending sale of NASDAQ listing
and infusion of new at board and leadership change to signify new Bioseparations
equity capital of USD team with additions direction business to KKR
85 MM, since April ongoing
2019
5
© 2019 Liminal BioSciences Inc.
Anticipated Major Milestones
2019 1H-2020 2022-2023
Expected commercial partnership Expected filing of amended BLA Expected completion of registration
for Ryplazim™ with FDA for Ryplazim™ (priority studies to support filings for PBI-
review) 4050 for ALMS in in global markets
6
© 2019 Liminal BioSciences Inc.Divestiture of Bioseparations business to KKR
• Sale of Bioseparations business (PBL) located in Isle-of-Man announced in Nov 2019 with closing expected in Q4-2019
• PBL has a 30 year track record in affinity chromatography contract services to global speciality pharma and biotech companies
• Annual revenue run-rate of approx. GBP16 MM with current breakeven profitability
• Total transaction value of up to GBP 45 MM
• Upfront payment expected on closing of approx. GBP 32 MM
• Remaining contingent payments of GBP 13 MM based on future sales performance of business
• Liminal to continue as a customer of PBL for materials required for Ryplazim™ manufacturing process
7
© 2019 Liminal BioSciences Inc.Expected Marketing Partnership for Ryplazim™
• Expected filing of amended BLA with FDA, in H1-2020, for approval of Ryplazim™ for congenital plasminogen deficiency
• Filing expected to be under priority review with PDUFA date in 2020
• European filing for Ryplazim™ to be commenced after expected US approval and launch
• Ongoing discussions to establish global commercial partnership for Ryplazim™ for launch in major markets
• Liminal will continue to manufacture Ryplazim™ and supply commercial partner for global sales from internal production facility
and contract manufacturing organizations in North America
8
© 2019 Liminal BioSciences Inc.Anti-Fibrotic Small Molecule
Therapeutics
PBI-4050 and PBI-4547
9
© 2019 Liminal BioSciences Inc.Building a Portfolio of Novel Antifibrotics
PBI-4050 Phase 3 expected to begin in 2020 to treat Alström Syndrome
(ALMS)
PBI-4050 Phase 2 in ALMS completed with demonstrated impact on fibrosis in
multiple organ systems.
PBI-4050 Phase 2 Respiratory Indications in 2020
Therapeutic Targets Additional clinical studies for respiratory indications to be commenced in 2020
supported by existing preclinical and clinical data
• Liver
PBI-4547 Phase 1 in healthy volunteers commenced H2-2019
• Renal
• Respiratory Disease The study has been suspended while the pharmacokinetic (“PK”) data for the
first three cohorts is obtained and reviewed. No safety issues or severe adverse
effects were observed in first three cohorts.
Additional clinical studies to be underway in 2020 and 2021
Additional clinical studies to explore potential in anti-fibrotic indications
in kidney disease with a new drug compound to be selected
10
© 2019 Liminal BioSciences Inc.Fatty Acids and Free Fatty Acid Receptor Family
• Free fatty acids (FFA’s) traditionally viewed as nutrients and metabolic substrates
• Deorphanization of several G protein coupled receptors (GPCR’s) during the 2000’s led to evidence of a role for FFA’s in
important signalling pathways primarily in metabolic disorders
• GPCR’s activated by FFA’s are categorized by ligand profile, long, medium or short-chain fatty acids (LCFA’s, MCFA’s or SCFA’s)
• FFAR1 (or GPR40) and FFAR (or GPR120) are two important targets as receptors for MCFA’s and LCFA’s
• GPR84 is a related receptor for MCFA’s with a role in the regulation of inflammation
• Liminal research has focused on mechanisms involving these three GPCR’s, compounds with multi-targeting effect and roles in
inflammation, metabolic disease and fibrosis
• Discovery engine has generated over 3,000 proprietary compounds with multi-target effect against FFAR’s
• Robust activity in broad panel of in vivo disease models confirmed for over 30 compounds
• Therapeutic areas of focus: system fibrosis conditions, respiratory disease, kidney disease and liver disease
11
© 2019 Liminal BioSciences Inc.PBI-4050: An Anti-inflammatory And Anti-
Fibrotic Agent
Demonstrated across multiple disease models in
Designed to reduce fibrosis via preclinical studies:
regulation of macrophages, • Chronic kidney disease (CKD);
fibroblasts/myofibroblasts, and epithelial • Diabetic kidney disease (DKD);
• Lung fibrosis, liver fibrosis;
cells
• Heart fibrosis, Crohn’s disease, scleroderma and
osteoporosis.
Profile well-established in [Phase 1
and 2] clinical studies; most Evaluated in over 250 subjects,
adverse events reported were mild dosed up to 1,200 mg daily, in 8
and discontinuations from clinical PBI-4050 clinical studies
studies to date have been rare
3-pentylbenzeneacetic acid sodium salt with a
Composition of matter patent
molecular weight of 228.3, derived from a
coverage in major markets until at
structure-activity study of sodium decanoate, a
least 2030
salt of the naturally-occurring medium-chain fatty
acid, decanoic acid
12
© 2019 Liminal BioSciences Inc.Lead Indication for PBI-4050: Alström
Syndrome (ALMS)
Rare autosomal recessive Fibroblasts with ALMS1
mutations in ALMS1 gene, mutations are resistant to
expressed in metabolic tissues apoptosis and secrete high
and in ciliated tissues levels of extracellular matrix
Progressive and severe fibrosis ALMS patient life expectancy
affecting heart, kidney, lungs rarely exceeds 50 years of age
and liver
Childhood onset with visual Early onset obesity with
dysfunction and hearing loss severe insulin resistance
13
© 2019 Liminal BioSciences Inc.Transforming ALMS Patient Care
No FDA or EMA approved treatments for ALMS patients
FDA granted both orphan drug designation and rare paediatric disease designation, EMA granted orphan drug status
and UK MHRA granted Promising Innovative Medicine (PIM) status for PBI-4050 in ALMS. Further potential to expand
clinical program to other rare diseases similar to ALMS
1200 12
ALMS patients showed
2020 1 st
PBI-4050 is a potential
Affected individuals a dramatic impact on Phase 3 clinical study
first-in-class therapy to
have been identified fibrosis in multiple expected to begin in
reduce fibrosis in ALMS
organ systems in Ph II 2020
worldwide patients
study
*Estimates have ranged from 1 in 10,000 to less than 1 in 1,000,000 individuals in the general population
14
© 2019 Liminal BioSciences Inc.Ph II Trial Design Summary
Completed Phase 2, Open-Label Study In Subjects With Alström Syndrome
(University Hospital of Birmingham, UK : National Center of Excellence for ALMS)
Study design Key Inclusion Criteria
Single-centre trial evaluating the safety and tolerability • Documented diagnosis of Alström syndrome, confirmed by
of multiple oral doses of 800 mg PBI-4050 genetic testing
• Age ≥ 16 years
• Subjects on diabetes treatment have stable background therapy
Screening PBI-4050 (800 mg od)* for at least 1 month
period
• Metabolic syndrome
Diagnosis
of ALMS E 24 weeks
Key Exclusion Criteria
18 subjects were planned for enrolment (E); 12 subjects enrolled • Uncontrolled hypertension with BP > 170/100 mmHg
After 24 weeks, subjects were eligible for a 36/48 week • AST/ALT level ≥ 5 × upper limit of normal (ULN)
extension period
15
© 2019 Liminal BioSciences Inc.Clinical Trial Endpoints
Primary endpoints Exploratory endpoints
Endpoints (cont.)
• Safety and tolerability
• Adipose tissue biopsy (Fat biopsy)
• Adverse Events (AEs)
• Clinical laboratory tests • Liver stiffness
• Vital signs (transient elastography, FibroScan)
• Physical exam
• Electrocardiogram • Liver MRI to assess liver fibrosis and fat content
Secondary endpoints • Cardiac MRI to assess cardiac fibrosis
• Diabetic/Metabolic Syndrome parameters • Hyperinsulinaemic-euglycaemic clamp
• Inflammatory/obesity markers in blood and urine (endogenous glucose, insulin, lipid dynamics)
• Antidiabetic dosage changes • 4-point glucose profile
(insulin-dependent subjects)
16
© 2019 Liminal BioSciences Inc.Reduction of Liver Stiffness in ALMS Subjects
FibroScan score reduced or stabilized in 10 out of 11 evaluable patients
Fibroscan Score 21.1
Cirrhosis Baseline
F4 17.1
Last available measurement
13.1
12.5
12.4
12.2
Severe Fibrosis
F3 10.4
9.9
9.5
8.8
8.6
Significant
Fibrosis
8.1
F2 7.8
7.6
7.4 7.5
7 6.6
6.1 6.0
5.5
5.1 5.1
Mild Fibrosis 5.0
4.6
F1
2.5
Fibroscan Fatty Liver
Score
Note: No baseline Fibroscan data available for one patient 17
© 2019 Liminal BioSciences Inc.Rollover Study Underway
Ongoing:
Open-Label Rollover Study of PBI-4050 in Subjects with Alström Syndrome at the specialist patient
management center in Birmingham (UK)
• Primary objectives: long term safety & tolerability
• Secondary objectives: effect on metabolic syndrome parameters & liver stiffness using FibroScan
• Up to 96 weeks of treatment
18
© 2019 Liminal BioSciences Inc.Changes In Cardiac T1 Observed Before And
After Treatment
*Richard Steeds et al manuscript in preparation
19
© 2019 Liminal BioSciences Inc.PBI-4050 ALMS Phase 3 Clinical Study Update
Several FDA Type C meetings held in Clinical study protocol to be finalized Investigators selected in North
2018 and 2019; final meetings with after final comments from FDA/EMA, America and Europe, and patient
FDA and EMA scheduled in Q1-2020 including primary endpoints as identification for study underway
agreed with FDA/EMA
Enrolment goal of approximately 45 Working with well-established Principal Investigator: Dr. Clair
ALMS subjects, 30 adults and 15 international ALMS patient advocacy Francomano, University of Indiana
paediatric, treated with 1200 mg of organizations to assist in conduct of
Investigator: Dr. Tarekegn Hiwot,
PBI-4050 dosed once daily study
University Hospital Birmingham, UK
Investigator: Dr. Pietro Maffei, Padua
Hospital, Italy
20
© 2019 Liminal BioSciences Inc.PBI-4547: A Differentiated Mechanism for
Treating Liver Fibrosis
Second clinical candidate developed as an
Phase 1 clinical study of PBI-4547
analogue of PBI-4050
commenced
Pre-clinical studies show that PBI-
Mechanism of action includes
4547 could be a potential treatment
GPR120 agonist in addition to being
for NASH with an effect on both
GPR84 antagonist and GPR40
liver fibrosis and metabolic disease
agonist
in patients
GPR120 agonists shown to improve Phase 1 clinical study paused after
insulin sensitivity third dose cohort to study PK results
21
© 2019 Liminal BioSciences Inc.Metabolic Reprogramming MoA: PBI-4547 Designed to
Promote -Oxidation and Mitochondrial Uncoupling
Fatty Acid
CD36
PBI-4547:
• Reduced insulin resistance Fatty Acid Fatty Acyl-CoA Glucose
in HFD mice Acetyl CoA
oxidation
• Observed to promote fatty Pyruvate
ACC MCD CPT1
acid β-oxidation in liver Glucose
MPC
Oxidation
from high-fat diet mice, Malonyl CoA CPT2 Fatty Acyl-CoA
Acetyl CoA PDH Pyruvate
resulting in reduced AMPK HADHA ACOX
steatosis Fatty Acid TCA PDK4
• Restored WAT homeostasis β-Oxidation Cycle NADH
Fatty acid FADH2
by reducing inflammation -oxidation H+ ADP H ATP IV
+ II H+
and fibrosis UCP ATPase
I
II I
H+
• Increased Ucp1 expression H+ H H
in WAT and Ucp2/3 in liver, + +
UPREGULATED
promoting mitochondrial Energy
expenditure/
proton leak and increasing browning UNCHANGED
overall energy expenditure
22
© 2019 Liminal BioSciences Inc.Overview of PBI-4547 Pre-clinical Evidence: NASH
NASH is a multi-faceted disease including metabolic dysregulation, chronic inflammation and fibrosis;
PBI-4547 displayed activity against each of these aspects in preclinical studies
In relevant animal models, PBI-4547 effects included:
• Metabolic regulation
• Improved lipid and glucose metabolism
• Increased fatty acid oxidation/ mitochondrial effects
• Anti-inflammatory activity
• Reduction of inflammatory cytokines
• Anti-fibrotic activity
• Reduction of stellate cell proliferation and activation
• Reduction of pro-fibrotic cytokines (CTGF, TGFβ, IL-6 and others)
• Reduction of fibrotic markers (collagen, α-SMA and others)
• Promotes matrix re-modelling and tissue regeneration
23
© 2019 Liminal BioSciences Inc.Summary of Key Pre-clinical Studies: NASH / Liver
Fibrosis
NASH / Metabolic Syndrome NASH / Metabolic Syndrome Liver Fibrosis
High-fat diet model: PBI-4547 Obese mouse model (ob/ob) : PBI- • CCL4 liver fibrosis mouse model:
improved glucose metabolism and 4547 reversed diabetes and metabolic PBI-4547 reduced the collagen
insulin resistance, and reduced liver syndrome through regulation of lipid/ content / level of liver fibrosis
damage: glucose metabolism, beta-oxidation
• Upper bile duct ligation model: PBI-
• Improved glucose metabolism by and fibrosis in liver and white adipose
4547 reduces the collagen content/
reducing insulin resistance and tissue:
preserving beta-cell function level of liver fibrosis
• Reduced blood glucose, cholesterol
• Reduced hepatic steatosis and and triglyceride levels
ballooning
• Reduced pro-inflammatory / pro-
• Reduced serum triglycerides and fibrotic markers in liver
increased adiponectin* levels
• Reduced adipocyte size and level of
• Regulated pro-inflammatory / fibrosis in white adipose tissue
fibrosis gene expression in liver
and adipose tissues • Increased serum adiponectin levels
*Adiponectin is produced by adipose cells. It helps to regulate glucose and lipid metabolism, improves insulin sensitivity and it also has anti-inflammatory
effects. Levels of adiponectin are inversely correlated with the presence and severity of metabolic diseases / dysfunction
24
© 2019 Liminal BioSciences Inc.Evidence for GPR84 / GPR40 Receptor Engagement
Knockout mouse studies with PBI-4547 are underway to elucidate the relative roles of GPR40, GPR84 & GPR120
Results available to date demonstrate GPR40 knockout studies are still GPR120 knockout mice showed
that GPR84 has a crucial role in the underway significantly increased TGF-β mRNA and
effect of PBI-4547 on: collagen type1α mRNA in the liver
• Glucose metabolism and insulin- compared to wild-type mice (i.e. had
sensitization more severe liver fibrosis)
• Lipid metabolism
• Liver cell ballooning
• However, the effect of PBI-4547 on
adiponectin levels is independent of
GPR84
25
© 2019 Liminal BioSciences Inc.Anticipated Future Clinical Studies with PBI-4547
Multiple ascending doses in healthy Dr. Stephen Harrison advising on
volunteers and patients with NAFLD future clinical studies planned for
or NASH PBI-4547
2020 to 2022
Phase 2a in NASH and an additional Phase 2b in NASH and/or an
liver fibrosis indication additional liver fibrosis indication
26
© 2019 Liminal BioSciences Inc.Summary of PBI-4547 in NASH and Liver Fibrosis
• Novel biological target with differentiated mechanism of action versus other current drugs under development
• Substantial preclinical data potentially supports the treatment of patients with conditions relating to metabolism disorders,
inflammation and liver fibrosis
• Presentations given at AASLD in November of preclinical data for PBI-4547
• Broad mechanism of action against multiple targets may be well-suited for NASH patients
• Combination studies with newly approved agents possible in future
• Other patient populations with liver fibrosis beyond NASH under consideration for future clinical study
• PBI-4547 selected specifically for development in liver disease due to presumed mechanism of action
• Strong IP protection on PBI-4547 and other back-up compounds
27
© 2019 Liminal BioSciences Inc.Anticipated Expansion of R&D Portfolio
• Expansion to study current novel pathway in FFAR’s and compounds in serious fibrosis in kidney disease (PBI-4610 and other
potential drug candidates)
• Novel targets and novel pathways beyond FFAR biology
• Novel technologies to expand current drug discovery engine
• Potential cquisition of clinical-stage compounds in current therapeutic areas of focus
28
© 2019 Liminal BioSciences Inc.Investment Summary
Late-stage pipeline with potential best-in-class drugs for fibrosis in treatment of liver, renal and respiratory diseases
Potential for first-in-class therapy for Exceptional leadership team and
PBI-4050 in ALMS and multiple board, with support from existing
opportunities for expansion and institutional investors
growth in respiratory disease and
systemic fibrosis
Clinical development plans ready to Ryplazim™ partnerships and strategic
execute, with milestones expected divestiture of PBL expected to
over next 12-36 months strengthen balance sheet in 2019 and
2020
29
© 2019 Liminal BioSciences Inc.What we do today,
will change lives
tomorrow.
30
© 2019 Liminal BioSciences Inc.You can also read
